Phenolic derivatives, such as catechol, guaiacol and syringol derivatives are naturally occurring compounds found in nature. Catechol moieties are often associated with mussel adhesive proteins (MAPs) which utilize this derivative to form tenacious bonds in aqueous solutions. Alternatively, guaiacol and syringol derivatives are often associated with plants, and form the structural components of lignins. These structural components are formed through the oxidative crosslinking of the phenolic group to form polymeric structures. It was found this oxidative process also forms covalent bonds between amines and thiols on tissue surfaces. As such, specific phenolics which allow for the incorporation of oxidants may be used as medical adhesives. The medical adhesives may be constructed into a thin film in which oxidant is incorporated directly into the polymer film allowing for strong interfacial binding to a support and tissue when hydrated.
Ferulic acid, sinapic acid and syringic acid adhesive endgroups are found naturally in plants, typically as structural components through an oxidative polymerization reaction to form lignins. Generally, the adhesive endgroups comprise a double bond between the phenolic ring and carboxylic acid. They contain at least 1 methoxy group (ferulic acid) and no more than two methoxy groups (sinapic acid and syringic acid). Methoxy groups may be preferable at the 3 position, or at both the 3 and 5-position. They also may contain at least one hydroxyl group, typically at the 4-position of the aromatic ring, and the methoxy group(s) are next to this hydroxyl group (3, or 3 and 5 position) such that hydroxyl group(s) may be switched with the methoxy group as, for example, in Medhesive-188, i.e., with isoferulic acid, wherein the hydroxyl group is at the 3-position while the methoxy group is at the 4 position. Accordingly, a hydroxyl group may be placed around the aromatic ring as well as up to two methoxy groups. Additionally, ferulic acid and sinapic acid may contain a double bond between the phenolic aromatic ring and the carboxylic acid. Compounds with carboxylic acids attached directly to the phenolic ring (e.g., benzoic acid derivatives) such as Medhesive 194 (i.e., syringic acid) may also be adhesive, even though they lack the double bond between the phenolic ring and carboxylic acid.
In medical practice, few adhesives exist which provide both robust adhesion in a wet environment and suitable mechanical properties to be used as a tissue adhesive or sealant. For example, fibrin-based tissue sealants (e.g. Tisseel VH, Baxter Healthcare) provide a mechanical match for natural tissue, but possess poor tissue-adhesion characteristics. Conversely, cyanoacrylate adhesives (e.g. Dermabond, Ethicon, Inc.) produce adhesive bonds with surfaces, but may be stiff and brittle with regard to mechanical properties and release formaldehyde as they degrade.
Therefore, a need exists for materials that overcome one or more of the current disadvantages.